简洁的,不对称的,立体控制的A,B类石素和B类诺托胺的总合成
Gerald D Artman1, Alan W Grubbs, Robert M Williams
1Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Journal of the American Chemical Society
|April 26, 2007
概括
这项研究简要地介绍了真菌代谢物斯蒂法西丁A,斯蒂法西丁B和诺托阿米德B的不对称总合成. 新的合成策略和微波加热被用来高效地制备这些复杂的分子.
科学领域:
- 有机化学 有机化学
- 自然产品的合成自然产品的合成
- 药用化学 医学化学
背景情况:
- 的代谢物,如石丁A,石丁B和诺托胺B,具有具有潜在生物活性的复杂结构.
- 有效和可扩展的合成途径对于进一步研究和这些化合物的潜在治疗应用至关重要.
研究的目的:
- 开发简洁和不对称的 (-) - 斯泰法西丁A, (+) - 斯泰法西丁B和 (+) - 诺托阿米德B的总合成.
- 建立适用于构建复杂自然产品的新型合成方法.
主要方法:
- 使用 (R) - 烯甲基的非对称合成.
- 开发一个修订的路线,用于pyranoindole核心.
- 交叉元论的应用,用于功能组的介绍.
- SN2'循环形成一个 [2.2.2] 桥梁式的自行车系统.
- 微波辅助合成以优化反应时间和产量.
主要成果:
- 取得了成功和简洁的 (-) - 斯泰法西丁A, (+) - 斯泰法西丁B和 (+) - 诺托阿米德B的不对称总合成.
- 使用微波加热有效合成关键中间体,从而提高了产量.
- 一种新的交叉元解策略和SN2'循环被验证用于构建复杂的分子架构.
结论:
- 开发的合成策略可以有效地获得重要的真菌代谢物.
- 使用的方法为合成相关的自然产品提供了多功能性.
- 这项工作有助于自然产品合成和药物发现领域.
相关概念视频
SN2 Reaction: Stereochemistry
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
SN1 Reaction: Stereochemistry
This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Diels–Alder reactions between cyclic dienes locked in an s-cis configuration and dienophiles yield bridged bicyclic products.
Preparation of 1° Amines: Gabriel Synthesis
Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is a method to obtain ketones from alkyl halides and β-keto esters. The reaction occurs in the presence of an alkoxide base that abstracts the acidic proton of the β-keto esters. The step results in an enolate ion which is doubly stabilized. The enolate then reacts with an alkyl halide via the SN2 process to produce an alkylated ester intermediate with a new C–C bond. The hydrolysis of the intermediate, followed by acidification, results in an alkylated β-keto acid.
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
The Diels–Alder reaction is one of the robust methods for synthesizing unsaturated six-membered rings. The reaction involves a concerted cyclic movement of six π electrons: four π electrons from the diene and two π electrons from the dienophile.

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